Histamine is a primary mediator of anaphylaxis, a neurotransmitter, and is now also known to be an immune modulator. Histamine suppresses the production of IL-2 and IFNg from TH1 T-cells, but up-regulates IL-5 synthesis from TH2 cells. The molecular mechanisms by which histamine acts are not known, but some of its immunomodulatory effects are through an elevation of intracellular cAMP. There is also evidence that both the inhibitory and stimulatory activity of histamine on T-cells is mediated through protein kinase-A (PKA). This application seeks to further define the cellular mechanisms associated with the immunoregulatory role of histamine. Using cloned murine helper T-cells and mouse splenocytes, the goal of this study is to assess: 1) the involvement of PKA in T-cell cytokine secretion and mRNA expression; and 2) assess the role of histamine on protein tyrosine kinase activity in cloned T-cells and splenocytes. This study will help define the molecular mechanisms of histamine's action on the immune response.